It is imperative to navigate this ideal carefully given the varying effects of pregnancy gestation on insulin sensitivity and the risk of iatrogenic hypoglycemia, especially if non-modified human insulin remains the mainstay of treatment.

The underlying reason for non-adherence was not determined. Diabetes-related knowledge, family support, fear of hypoglycemia, socioeconomic status, and insulin delivery devices have all been implicated as contributors to non-adherence Based on our daily clinical practice, all of these factors, either individually or collectively, may contribute to non-adherence and insulin discontinuation, with hypoglycemia often cited by patients as a major reason for discontinuing insulin or diverting from the prescribed insulin regimen.

In pregnant women with diabetes and imminent preterm delivery, betamethasone therapy enhances fetal lung maturation but also causes hyperglycemia and even DKA.

Rigorous implementation of glycemic monitoring and appropriate correction of hyperglycemia are of paramount importance to prevent DKA events in these women In the index study, a near quarter of women were diagnosed with diabetes at the time of the DKA event.

Due to limited resources and access to health care locally, many pregnant women enter formal heath care for the first time during pregnancy.

Further, although universal screening of glucose homeostasis during pregnancy would be ideal, our public health sector currently lacks the resources to do.

Selective screening is therefore practiced in many regions within South Africa including the Western Cape, where the modified NICE criteria are used The majority of women in our study were not tested timeously, despite having risk factors that dictated selective screening.

Based on BMI alone, more than two thirds of our cohort qualified for an OGTT at 24 weeks to screen for GDM 41 , Our data, albeit limited, indicate that antenatal selective screening of glucose homeostasis is not implemented optimally, supporting the opinion that screening practices in South Africa remain limited 6 , In addition, less than half of the cohort with known diabetes underwent trimester-specific HbA1c measurements to aid antenatal glucose monitoring.

A high median HbA1c of Both undiagnosed diabetes and poor glycemic control are very likely to have enhanced the risk of DKA events in our patient cohort, irrespective of the identified precipitating causes.

These results concur with historic reports 9. As most of the spontaneous intrauterine deaths occurred at the time of the DKA, the hypothesis that the DKA contributed significantly is supported. However, to what extent maternal acidosis, dehydration with reduced uteroplacental perfusion, electrolyte imbalance per se or a combination of these factors contributed, remains unclear.

Prior studies have shown that the risk of stillbirth increases with the severity of maternal acidosis 10 , 32 , 33 , 44 , a finding that we were unable to confirm. According to the study, fetal demise rates are higher in pregnancies complicated by DKA than in more recent studies in developed countries such as the United States and the United Kingdom 32 , Every year an estimated 2.

Stillbirth has multifactorial etiologies. Increased maternal age and BMI are established risk factors, whereas hypertension and diabetes, especially if poorly controlled, are the most common maternal conditions known to contribute 45 — As stillbirths occur more frequently in low and middle income countries, low socio-economic status and poor access to formal health care are regarded as significant contributors Many of these established contributors were highly prevalent in our study population but appeared similar between pregnancies with live births and those with fetal loss.

The small numbers in our study, however, precluded us from drawing firm statistical conclusions. In our study, hypokalemia and hypoglycemia, which may result in arrhythmias, respiratory failure, and fetal fatalities, were common consequences of DKA treatment 48 — Hypokalemia was shown to be significantly associated with fetal loss.

The prevalence of obesity amongst South African women of childbearing age is concerning and escalating The mechanism that underlies the observed association between obesity and stillbirth remains elusive and multifactorial.

Obese women are more likely to develop gestational hypertension and diabetes and is associated with an increased risk of apnoeic-hypoxic events, as well as the development of uteroplacental insufficiency earlier in pregnancy 52 , A study conducted in sub-Saharan Africa found that obese Zimbabwean women had a seven fold increased risk of preeclampsia and a fivefold increase in T2D OR 5.

Diabetes is one of the major causes of stillbirths worldwide. A significant correlation exists between the metabolic control of the mother during pregnancy and the adverse outcomes for hyperglycemic pregnancies Uncontrolled diabetes in early gestation, especially if present in the first few weeks, adversely impacts placental growth and development and predispose to intra-uterine growth restriction 56 — Hyperglycemia causes endothelial dysfunction, which contributes to the development of hypertensive conditions such as pre-eclampsia during pregnancy 47 , Both these conditions are known to contribute to the risk of fetal demise irrespective of hyperglycemia.

Pre-DKA HbA1c values were unacceptable for both live-births and fetal losses in this cohort, indicating suboptimal diabetes management and compliance. As we had uniform uncontrolled hyperglycemia, we were unable to determine the degree to which hyperglycemia itself contributed to perinatal mortality.

Discordant fetal growth in the setting of diabetes in pregnancy is also associated with fetal demise. Maternal overweight, the degree of maternal hyperglycemia, gestational weight gain, and maternal lipids all contribute to fetal overgrowth In contrast, poorly controlled diabetes may result in intrauterine growth restriction due to suboptimal placental development if present in early gestation and may also result in growth restriction if associated with established microvascular disease 56 , In our study, maternal glucose control was poor, yet only a single baby was classified as macrosomic.

While gestational age could be a confounder, hyperglycemia in women with pre-existing diabetes may have caused placental insufficiency rather than excessive growth and macrosomia in our study. The clinical course of diabetes types is known to vary greatly, and there is evidence that some patients with adult-onset diabetes share characteristics of both T1D and T2D T1D is, however, considered to be an autoimmune disease caused by autoantibodies against pancreatic β-cells The presence of anti-GAD antibodies has also been shown to be predictive of the onset of postpartum diabetes in women with GDM Despite reports that genotypes differ according to ethnicity, Padoa found no ethnic difference between black Africans and white persons with T1D in South Africa Anti-GAD antibodies were tested in twenty-one women without known T1D at the time of DKA in our study.

These included 14 with HFDP and seven women with a prior diagnosis of T2D. In light of these findings, we believe that pregnant women with DKA should be strongly considered for auto-immune diabetes regardless of their BMI or prior classification as T2D.

Knowledge of anti-GAD antibody status in this subset of pregnant mothers may be particularly useful to determine insulin dependency or in identifying women who might benefit from emerging treatments for the prevention of T1D. In our background reproductive female population, we have a heavy metabolic footprint and obesity is a specific concern.

There is some controversy as to whether obesity trends in the general population are indicative of obesity rates in people with T1D, or whether they are related by genetics and environmental susceptibilities 68 , Nearly half of women with T1D who had a DKA event in pregnancy in our study were overweight or obese, thus warning against reliance on clinical phenotype to dictate diabetes subtyping.

The findings of this study are consistent with recent findings from other studies that indicate that obesity is a highly prevalent problem in individuals with T1D 68 — According to Evertsen et al. Most women in our cohort had some form of hypertension. Surprisingly neither hypertension nor pre-eclampsia were present in any of their pregnancies with fetal loss DKAs in pregnancy have rarely been studied in detail at the patient level.

Due to the retrospective and descriptive nature of this study, causality cannot be inferred, however, it contributes to the current knowledge of pregnancy outcomes and complications associated with DKA.

The small sample size prohibited robust statistical analysis. Furthermore, neither the specific socioeconomic status of the participants nor their competency in managing their diabetes were formally assessed. The high rates of obesity and hypertensive disorders, as well as suboptimal antenatal glycemic control, potentially contributed to the high number of intrauterine deaths observed.

Significant implementation gaps remain in screening for hyperglycemia and antenatal diabetes care in resource-constrained environments.

These gaps must be eliminated if dangerous complications like DKA are to be minimized Clinicians should strive to ensure continuous development and implementation of strategies that ensure optimal preconception and antenatal management of diabetes, as well as empowering women with diabetes through education.

Unintended iatrogenic consequences of DKA management such as hypokalemia and hypoglycemia should be minimized with strict protocols to limit the possibility of fetal loss.

In the context of high-risk populations for DKA and healthcare providers, we emphasize the importance of ongoing structured diabetes education. Through the use of these data, local practices can develop targeted protocols and interventions that can decrease the risks associated with hypokalemia, ultimately improving patient outcomes and inspiring a culture of continuous improvement.

This study found a high risk of fetal mortality and undiagnosed auto-immune diabetes in women with DKA during pregnancy. There was a strong correlation between hypokalemia and fetal loss, suggesting a window of opportunity for addressing management gaps.

The datasets presented in this study can be found in online repositories. The study complied with the World Medical Association Declaration of Helsinki.

The studies were conducted in accordance with the local legislation and institutional requirements. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

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Fortunately, there were no maternal deaths. However, Cases were defined as euglycemic DKA if the maximum recorded venous glucose concentration was less than Egan concludes: "The results of this study highlight that maternal and neonatal morbidity and high rates of pregnancy loss remain a significant problem.

Women presenting with DKA had suboptimally controlled diabetes, before and during pregnancy, and were from lower socioeconomic groups. At-risk pregnant women should be effectively counseled on the risks and adverse consequences of DKA , with education and support ideally commencing pre-pregnancy.

Furthermore, timely recognition and management of DKA in pregnancy are crucial for optimizing outcomes. Future work should focus on optimizing prevention strategies in high-risk women.

Dhanasekaran M, et al. Diabetic ketoacidosis in pregnancy: Clinical risk factors, presentation, and outcomes. Refer a patient to Mayo Clinic. This content does not have an English version. This content does not have an Arabic version. Diabetic ketoacidosis in pregnancy poses mortality risk.

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Conclusion: Nausea and vomiting is a prominent presenting feature of DKA in pregnancy. With aggressive insulin and resuscitation, hyperglycemia and acidosis improve rapidly. With current treatment, good perinatal outcomes can be expected.

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